UTHSC Researchers Draw National Attention for Findings that Could Lead to Possible Treatment for Those with Most Severe Form of Multiple Sclerosis

Written by Communications and Marketing

| January 24, 2014

Dr. Lidia Gardner and Dr. Michael Levin are researching Apolipoprotein A1, or ApoA1, and its relationship to Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating neurological disease that affects 2.3 million people worldwide, a number that has gone up 10 percent in the past five years. New medications have greatly improved the lives of those with relapsing-remitting MS, the milder form of the disease. But for the sickest MS patients, those with the progressive form of the disease, there has been little in the way of treatment.

Findings from a new study by researchers at the University of Tennessee Health Science Center (UTHSC) may be a key to developing treatments for those with the chronic, progressive form of the disease.

Research conducted by Dr. Lidia Gardner, PhD, assistant professor of Neurology at UTHSC, found that patients with progressive MS have lower levels of Apolipoprotein A1, or ApoA1, a protein that is the main component in High Density Lipoprotein (HDL), or good cholesterol. Dr. Gardner conducted the research over the course of a year and half in the lab of Michael Levin, MD, professor of Neurology, and of Anatomy and Neurobiology at UTHSC, and chief of Neurology Services at the Memphis Veterans Affairs Medical Center.

Dr. Gardner was selected to present her findings at a press conference during the Society for Neuroscience annual meeting in San Diego. The meeting attracts more than 30,000 people from around the world. She is now working to get the study published in a peer-reviewed journal.

Dr. Gardner said ApoA1 is known to be protective against inflammation, a key sign of this autoimmune disease that results when the body’s immune cells attack the nervous system. “The bottom line is sustaining normal ApoA1 levels could be beneficial for multiple sclerosis patients,” she said. “It is well known that MS patients experience fatigue and suffer from memory loss and other cognitive problems. Other studies have shown that high levels of ApoA1 might benefit cognition.”

The research, funded primarily by the National Multiple Sclerosis Society, analyzed blood samples taken from MS patients with different types of the disease, as well as from healthy subjects. Looking at the plasma, the ApoA1 levels were compared. Those with the progressive form of the disease, usually the older and more debilitated patients, showed the lowest levels of ApoA1, she said.

It is not clear why this is the case, but it is known that HDL levels decrease with age. HDL molecules consist of about 80 percent ApoA1 and 20 percent other apolipoproteins.

“The next step is to research and try to help those patients not to lose this protein,” Dr. Gardner said. “We also think there might be a correlation between the disease progression and the loss of the protein.”

The ApoA1 protein has been indicated in other neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. “We think that it is very important to sustain normal levels of ApoA1 protein and see if this will prevent patients from getting worse over time,” Dr. Gardner said.

A healthy diet aimed at maintaining or raising HDL cholesterol is a good idea in general, but probably not the answer to controlling ApoA1 levels. “Diet alone has never been shown to alter the natural history of MS,” Dr. Levin said.

Dr. Levin said 10 drugs are now approved for treating the relapsing-remitting form of MS, which is the most common. “And it’s left us with this other group of patients, for whom the medicines don’t work, that have this progressive form of MS, where ApoA1 is the lowest,” he said. “So maybe it’s a clue to certain therapies that would also help this second, sicker group of patients.”

Drs. Gardner and Levin believe they must first better understand the mechanisms of the protein and how it operates so medications can be developed.